Sofosbuvir and daclatasvir compared with standard of care in the treatment of patients admitted to hospital with moderate or severe coronavirus infection (COVID-19): a randomized controlled trial

Abstract Background Currently no effective antiviral therapy has been found to treat COVID-19. The aim of this trial was to assess if the addition of sofosbuvir and daclatasvir improved clinical outcomes in patients with moderate or severe COVID-19. Methods This was an open-label, multicentre, randomized controlled clinical trial in adults with moderate or severe COVID-19 admitted to four university hospitals in Iran. Patients were randomized into a treatment arm receiving sofosbuvir and daclatasvir plus standard care, or a control arm receiving standard care alone. The primary endpoint was clinical recovery within 14 days of treatment. The study is registered with IRCT.ir under registration number IRCT20200128046294N2. Results Between 26 March and 26 April 2020, 66 patients were recruited and allocated to either the treatment arm (n = 33) or the control arm (n = 33). Clinical recovery within 14 days was achieved by 29/33 (88%) in the treatment arm and 22/33 (67%) in the control arm (P = 0.076). The treatment arm had a significantly shorter median duration of hospitalization [6 days (IQR 4–8)] than the control group [8 days (IQR 5–13)]; P = 0.029. Cumulative incidence of hospital discharge was significantly higher in the treatment arm versus the control (Gray’s P = 0.041). Three patients died in the treatment arm and five in the control arm. No serious adverse events were reported. Conclusions The addition of sofosbuvir and daclatasvir to standard care significantly reduced the duration of hospital stay compared with standard care alone. Although fewer deaths were observed in the treatment arm, this was not statistically significant. Conducting larger scale trials seems prudent.

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AYUSH-64 as an adjunct to Standard Care in mild to moderate COVID-19: An open-label randomized controlled trial in Chandigarh, India

10.31219/osf.io/xyuas ◽

2021 ◽

Author(s):

Harbans Singh ◽

Sumit Shrivastva ◽

Babita Yadav ◽

Amit Kumar Rai ◽

Sophia Jameela ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Inflammatory Markers ◽

Standard Care ◽

Controlled Trial ◽

Control Group ◽

Rt Pcr ◽

Open Label ◽

Clinical Recovery ◽

Randomized Controlled ◽

Significant Difference

Background: There is limited evidence on the safety and efficacy of administering Ayurveda interventions as add-on to the standard care for COVID-19. Objective: To explore the therapeutic efficacy and safety of AYUSH-64 as an add-on to standard care in the management of mild to moderate stage COVID-19.Design, setting, participants and interventions: This was an open-label randomized controlled trial with 80 patients of mild to moderate stage COVID-19. Participants in the AYUSH-64 add-on group received two tablets (500 mg each) three times daily for 30 days along with conventional standard care (Paracetamol, Cetirizine, Vitamin C, and Azithromycin). The control group received standard care alone. Main outcome measures: The primary outcome assessed was the proportion of participants with clinical recovery and negative RT-PCR assay for COVID-19 on day 7, 15, 23, and 30. Additionally, change in pro-inflammatory markers, metabolic functions, HRCT chest and incidence of Adverse Drug Reaction (ADR) / Serious Adverse Event (SAE) were assessed.Results: Statistically significant difference was observed in the proportion of participants with clinical recovery in the AYUSH-64 add-on group (p<0.001) at each of the scheduled follow-up visits. All the participants in the AYUSH-64 add-on group clinically recovered by day 23 compared to 32.4 per cent in the control group. The mean duration for clinical recovery in AYUSH-64 add-on group (5.8 ± 2.67 days) was less as compared to control group (10.0 ± 4.06 days). The proportion of participants who turned RT-PCR negative for COVID-19 on day 7, 15, and 23 were 81.8, 94.5, and 100 per cent in AYUSH-64 add-on group, and 79.4, 94.5, and 97.2 per cent in control group, however, the difference observed was statistically not significant (p=0.314). The proportion of participants with improvement in HRCT chest was statistically significant in AYUSH-64 add-on group (p=0.031) unlike in control group (p=0.210). Similar reductions in most inflammatory markers measured (IL-6, CRP, Serum ferritin, and LDH) on day 30 (p<0.05) were observed in both groups. Conclusion: AYUSH-64 as adjunct to standard conventional care is safe and hastens clinical recovery in adult patients with mild to moderate COVID-19.

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Safety and Efficacy of Repurposed Siddha Medicines in Mild, Moderate, and Severe COVID-19 Patients Admitted To a Government Tertiary Hospital Near Chennai, Tamil Nadu– An Open-Labeled, Randomized, Controlled Trial.

10.21203/rs.3.rs-999914/v1 ◽

2021 ◽

Author(s):

Christian G J ◽

Meenakumari Ramasamy ◽

Shanthimalar Ramalingam ◽

Sankar Ganesan ◽

Ravichandran Vadugam Muthusamy ◽

...

Keyword(s):

Treatment Group ◽

Standard Care ◽

Tamil Nadu ◽

Controlled Trial ◽

Standard Of Care ◽

Tertiary Hospital ◽

Control Group ◽

Open Label ◽

Randomized Controlled ◽

Oxygenation Status

Abstract BackgroundCOVID-19 resulted in loss of human lives owing to respiratory failure caused by dysregulated immune system. Though many treatments are evaluated, the most appropriate is yet to be established. We hypothesized accelerated recovery and reduced mortality in mild, moderate and severe COVID-19 with Siddha regimen consisting of natural products.MethodsIn a randomized, controlled open-label trial conducted on 200 hospitalized COVID-19 patients, they were allocated equally to be treated with add-on Siddha regimen with Standard care or only standard care. The primary and secondary end points were accelerated recovery (≤ 7 days) and mortality comparison between the groups respectively. Patients were followed through 90 days.ResultsIn this study the accelerated recovery was 59.0% and 27.0% in treatment and control group (ITT analyses) (p < 0.001) respectively and Odds for it were four times higher in the treatment group (OR: 3.9; 95% CI: 1.9, 8.0). The estimated median time for recovery in the treatment group was 7 days (95% CI: 6.0, 8.0; p=0.003) and 10 days (95% CI: 8.7, 11.3) in control. Hazard ratio for death in control was 2.3 times that of treatment group. No adverse reactions or alarming laboratory values were observed in response to intervention. In severe treatment group (n=80), mortality was 15.0% and 39.5% in control (n=81). The COVID stage progression was 65% less in treatment group.ConclusionSiddha regimen demonstrated that they can synergistically improve oxygenation status, enhance the recovery rate and reduce the mortality better as compared to only Standard of Care.

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Convalescent plasma for hospitalized patients with COVID-19 and the effect of plasma antibodies: a randomized controlled, open-label trial

10.1101/2021.06.29.21259427 ◽

2021 ◽

Author(s):

Philippe Bégin ◽

Jeannie Callum ◽

Erin Jamulae Jamula ◽

Richard Cook ◽

Nancy M Heddle ◽

...

Keyword(s):

Primary Outcome ◽

Controlled Trial ◽

Harmful Effect ◽

Standard Of Care ◽

Hospitalized Patients ◽

Open Label ◽

Serious Adverse Events ◽

Randomized Controlled ◽

Negative Results ◽

Intent To Treat

The efficacy of convalescent plasma for COVID-19 is unclear. While most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content may influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 days of respiratory symptom onset. Patients were allocated 2:1 to 500 mL of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 days. The effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. 940 patients were randomized and 921 patients were included in the intent-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) in the convalescent plasma arm and 86/307 (28.0%) in the standard of care arm; relative risk (RR) 1.16 (95% confidence interval (CI) 0.94-1.43; p=0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% vs. 26.4%; RR=1.27, 95% CI 1.02-1.57, p=0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standard log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (OR=0.74; 0.57-0.95 and OR=0.66; 0.50-0.87, respectively), while IgG against the full transmembrane Spike protein increased it (OR=1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 days among hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavourable antibody profiles may be associated with worse clinical outcomes compared to standard care.

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Baidu Jieduan granule, traditional Chinese medicine, in the treatment of moderate coronavirus disease-2019 (COVID-19): study protocol for an open-label randomized controlled clinical trial

10.21203/rs.3.rs-44542/v2 ◽

2020 ◽

Author(s):

Wen Zhang ◽

Qin Xie ◽

Xiaoming Xu ◽

Shuting Sun ◽

Tian Fan ◽

...

Keyword(s):

Clinical Trial ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Controlled Trial ◽

Theory And Practice ◽

Control Group ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Open Label ◽

Randomized Controlled

Abstract Background: Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive impact on human health. Due to the absence of antiviral medicine for COVID-19 thus far, it is desperately need to develop the effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, hoping to produce clinical efficacy and decrease the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Baidu Jieduan granule in curing COVID-19. Methods/design: This multicenter, open-label randomized controlled trial is conducted 300 cases with COVID-19. The patients will be randomly (1:1) divided into treatment group or control group. All cases will receive standard therapy at the same time. The experiment group will receive Baidu Jieduan granule treatment twice a day for 14 days. The outcomes are assessed at baseline and at 3, 5, 7, 14 days after treatment initiation. The primary outcome is the rate of symptom (fever, fatigue, and coughing) recovery. Adverse events (AEs) will be monitored throughout the trial.Discussion: The study will provide a high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan granule in treatment of moderate COVID-19, and also enrich the theory and practice of TCM in treating COVID-19. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000029869. Registered on 15 February 2020

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Baidu Jieduan granules, traditional Chinese medicine, in the treatment of moderate coronavirus disease-2019 (COVID-19): study protocol for an open-label, randomized controlled clinical trial

Trials ◽

10.1186/s13063-021-05418-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wen Zhang ◽

Qin Xie ◽

Xiaoming Xu ◽

Shuting Sun ◽

Tian Fan ◽

...

Keyword(s):

Clinical Trial ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Controlled Trial ◽

Theory And Practice ◽

Control Group ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Open Label ◽

Randomized Controlled

Abstract Background Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive effects on human health. Due to the absence of antiviral medicine for COVID-19 thus far, there is a desperate need to develop effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, with the aim of achieving clinical efficacy and decreasing the use of antibiotics and glucocorticoids. The aim of this study was to evaluate the efficacy and safety of Baidu Jieduan granules in treating COVID-19. Methods/design This multicentre, open-label, randomized controlled trial will be conducted in 300 patients with COVID-19. The patients will be randomly (1:1) divided into a treatment group and a control group. All patients will receive standard therapy at the same time. Patients in the experimental group will receive Baidu Jieduan granule treatment twice a day for 14 days. The outcomes will be assessed at baseline and at 3, 5, 7 and 14 days after treatment initiation. The primary outcome will be the rate of symptom (fever, fatigue and coughing) recovery. Adverse events (AEs) will be monitored throughout the trial. Discussion The study will provide high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan granules in the treatment of moderate COVID-19, and enrich the theory and practice of TCM in treating COVID-19. Trial registration Chinese Clinical Trial Registry ChiCTR2000029869. Registered on 15 February 2020

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Baidu Jieduan Granule in the Treatment of Coronavirus Disease-2019 (COVID-19): Study Protocol for an Open-Label Randomized Controlled Clinical Trial

10.21203/rs.3.rs-44542/v1 ◽

2020 ◽

Author(s):

Wen Zhang ◽

Qin Xie ◽

Xiaoming Xu ◽

Shuting Sun ◽

Tian Fan ◽

...

Keyword(s):

Clinical Trial ◽

Controlled Trial ◽

Theory And Practice ◽

Control Group ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Clinical Trial Registry ◽

Open Label ◽

Randomized Controlled ◽

Epidemic Diseases

Abstract Background: Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive impact on human health. Due to the absence of antiviral medicine for COVID-19 thus far, it is desperately need to develop the effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, hoping to produce clinical efficacy and decrease the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Baidu Jieduan Granule in curing COVID-19. Methods/design: This multicenter, open-label randomized controlled trial is conducted 300 cases with COVID-19. The patients will be randomly (1:1) divided into treatment group or control group. All cases will receive standard therapy at the same time. The experiment group will receive Baidu Jieduan Granule treatment twice a day for 14 days. The outcomes are assessed at baseline and at 3, 5, 7, 14 days after treatment initiation. The primary outcome is the rate of symptom (fever, fatigue, and coughing) recovery. Adverse events will be monitored throughout the trial.Discussion: The study will provide a high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan Granule in treatment of severe COVID-19, and also enrich the theory and practice of TCM in treating COVID-19. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000029869. Registered on 15 February 2020

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A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19)

10.1101/2020.07.08.20148841 ◽

2020 ◽

Cited By ~ 6

Author(s):

Cheng-Pin Chen ◽

Yi-Chun Lin ◽

Tsung-Chia Chen ◽

Ting-Yu Tseng ◽

Hon-Lai Wong ◽

...

Keyword(s):

Retrospective Study ◽

Medical Records ◽

Controlled Trial ◽

Standard Of Care ◽

Public Hospitals ◽

Control Group ◽

Rt Pcr ◽

Open Label ◽

Viral Shedding ◽

Randomized Controlled

Objective In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. Methods Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ 400 mg twice for 1 d and HCQ 200 mg twice daily for 6 days were administered. Both study group and controlled group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020. Results There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1-9 days) and 10 days (95% CI; 2-12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70). Conclusions Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.

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Efficacy and safety of Guhong injection for treating the Coronary microvascular disease: study protocol for a randomized controlled trial

10.21203/rs.2.13551/v1 ◽

2019 ◽

Author(s):

Jieqin Zhuang ◽

Shuling Liu ◽

Hairong Cai ◽

Xingzhen Dai ◽

Yanhong Chen ◽

...

Keyword(s):

Clinical Trial ◽

Cardiovascular Diseases ◽

Controlled Trial ◽

Microvascular Disease ◽

Control Group ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Open Label ◽

Double Blind ◽

Randomized Controlled

Abstract Background: Coronary microvascular disease (CMVD) refers to cardiovascular diseases with normal coronary angiography but evidence of myocardial ischemia or microcirculation lesions, often presenting as angina pectoris attack. Coronary artery of microtubules dysfunction is one of the pathogenesis of coronary heart disease,but the occurrence and development and the current of CMVD intervention therapy remains to be further researched.Chinese traditional medicine (TCM)has advantages in the treatment of cardiovascular diseases, therefore, this article describes an ongoing randomized controlled clinical trial, based on the theory of TCM, for the purpose of evaluating the efficacy and safety of Guhong injection ,a Chinese patent medicine,compared with placebo in patients suffering from CMVD. Methods/design: This is a multicenter, randomized, parallel arm, open-label, double-blind, placebo-controlled clinical trial. A total of 260 eligible patients will be allocated and randomly assigned, in a ratio of 1:1, to either the experimental group or the control group. The treatment course is 10 consecutive days, with a 8-week follow-up. The primary outcome is the frequency of angina attacks, Secondary outcomes include myocardial metabolites, ecg changes, quantitative score of TCM syndromes, inflammatory response and endothelial function indicators. Discussion: This trial is strictly designed in accordance with principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide high quality evidence on the efficacy and safety of Guhong injection in the treatment of CMVD. Trial registration: Chinese Clinical Trials Registry, ChiCTR1900022902. Registered on 27 April 2019.

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Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial

Nature Medicine ◽

10.1038/s41591-021-01488-2 ◽

2021 ◽

Cited By ~ 3

Author(s):

Philippe Bégin ◽

Jeannie Callum ◽

Erin Jamula ◽

Richard Cook ◽

Nancy M. Heddle ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Primary Outcome ◽

Controlled Trial ◽

Harmful Effect ◽

Standard Of Care ◽

Hospitalized Patients ◽

Open Label ◽

Serious Adverse Events ◽

Randomized Controlled ◽

Negative Results

AbstractThe efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

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Effectiveness and Safety of Niclosamaide as Add-on Therapy to the Standard of Care Measures in COVID-19 Management: Randomized controlled clinical trial

10.1101/2021.06.10.21258709 ◽

2021 ◽

Author(s):

Ahmed S. Abdulamir ◽

Faiq I. Gorial ◽

Sattar J Saaedi ◽

Mohammed Fauzi Maulood ◽

Hashim Ali Hashim ◽

...

Keyword(s):

Clinical Trial ◽

Survival Rate ◽

Viral Infections ◽

Standard Of Care ◽

Antiviral Effect ◽

Control Group ◽

Controlled Clinical Trial ◽

Open Label ◽

Randomized Controlled ◽

Experimental Group

Background: COVID-19 pandemic has ignited the urge for repurposing old drugs as candidate antiviral medicines to treat novel challenges of viral infections. Niclosamide (NCS) is an anti-parasitic drug of known antiviral potential. Therefore, this study attempts to investigate the antiviral effect and safety of NCS on SARS-CoV-2 caused COVID-19 patients. Methods: Randomized controlled open label clinical trial encompassed 75 COVID-19 patients treated with standard of care plus NCS were included as experimental group and 75 COVID-19 patients treated with only standard of care therapy as control group. Each group was composed of 25 mild, 25 moderate and 25 severe patients. Survival rate, time to recovery, and side effects were the main endpoints for the assessment of the therapeutic effect and safety of NCS. Results: NCS did not enhance survival rate as three of severe COVID-19 patients in NCS and in control groups died (P>0.05). However, NCS, compared to control group, reduced the time to recovery in moderate and severe COVID-19 patients about 5 and 3 days, respectively but not in mild patients (P≤0.05). Most interestingly, NCS lowered time to recovery up to five days in patients with co-morbidities (P≤0.05) whereas only one day lowered in patients without co-morbidities (P>0.05). Conclusion: It is concluded that NCS accelerates time to recovery about 3 to 5 days in moderate to severe COVID-19 patients especially those with co-morbidities; hence, NCS is of clinical benefit for freeing hospital beds for more patients in pandemic crisis.

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